We have engaged in research directed at the study of endogenous and exogenous physiological and pharmacological effectors of upper gastrointestinal activity, both inhibitory and stimulatory, and including the areas of motility and secretion. Work with insulin and 2-deoxy-D-glucose (2-DG) in diabetic dogs has permitted us to pursue extensive evaluation of the relationships between blood/serum electrolyte levels and the initiation of vagal secretory and motor activity and has provided us with new insights into central vagal nervous system function. Since only scant information is available on gastric, pancreatic, and liver physiology in chronic diabetes, our direction during the past year has now been to combine our experience in the study of the physiology of these organs with a newer approach utilizing our experience with the diabetic animal, as well. We have found the diabetic animal to be a particularly practical model for the investigation of these phenomena and, concomitantly, we have developed a technique for pharmacologic continuous vagal stimulation using 2-DG, so that techniques are now available to us for the study of sustained vagal, gastrin, and histamine effect on upper gastrointestinal function. Our aims, therefore, continue to be limited to three areas: (A) Gastric, pancreatic, and biliary physiology in the chronic diabetic animal; (1) in the presence of acute and sustained acidosis with particular attention to homeostatic compensating mechanisms by the specified organs; (2) gastric secretory physiology with regard to the possible deleterious and decompensating effects of chronic diabetes. (B) Clarification of the interdependence and/or interrelationships of vagal and gastrin effects on the upper gastrointestinal tract with special emphasis on pancreatic and biliary tract secretion. (C) Fatigability in the normal pancreatic and biliary exocrine mechanisms in response to sustained vagal and/or gastrin stimulation. Finally, most recently, we have begun investigating the efficacy of the so-called Hollander test in the presence of partial vagotomy, with special investigation of differences in response between antrectomized and nonantrectomized but "drained" stomachs.